Hypercapnea

Etiology

At its root, hypercapnia is caused by either increased CO2 production metabolically or Respiratory failure. Metabolic processes that increase CO2 production may include fever, thyrotoxicosis, increased catabolism seen in sepsis or steroid use, overfeeding, metabolic acidosis, and exercise. Respiratory failure in this pathology is a failure to eliminate CO2 from the pulmonary system, which is synonymous with hypoventilation secondary to decreased respiratory rate or decreased tidal volume.[4] This is from decreased central nervous system respiratory drive, anatomical defects, decreased neuromuscular response, or increased dead space within the lung. It is also technically possible to develop hypercapnia through exposure and inhalation of environmental air rich in CO2. Depending on the etiology, hypercapnia can be an acute process or a chronic process. These can be distinguished through evaluation of the pH. [5]Acute hypercapnia will have PaCO2 elevated above the normal reference range of 45 mm Hg, and the HCO3 level will be within normal limits at approximately 30 mm Hg with a resulting proportional decrease in pH on blood gas evaluation below 7.35. Chronic hypercapnia allows for renal compensation to the elevated CO2 levels within the blood. As a result, PaCO2 will be elevated above the normal reference range of 45 mm Hg and the HCO3 level will also be elevated proportionally resulting in a less severe pH imbalance in the low-normal range. It is also to have an acute-on-chronic etiology that creates a combined picture with elevated PaCO2 and elevated HCO3 with an abnormal, decreased pH below 7.35.[6][7][8][9]

Epidemiology

Hypercapnia is a syndrome of illness rather than a single disease etiology. As such the exact epidemiology is linked to the specific inducing pathology. 

Pathophysiology

One of the purposes of the pulmonary system is to remove CO2 from the body through gas diffusion. This requires a diffusion gradient from the high concentration arteriolar blood into the relatively low concentration environmental air.  As such, the CO2 gradients are developed and maintained where PaCO2 in arterial blood is directly proportional to the rate of CO2 metabolic production and inversely related to the rate of CO2 elimination by the lung via increased alveolar ventilation. Alveolar ventilation is the removal of alveolar air into the environment, defined as the expired minute volume that reaches the alveoli and is determined by minute ventilation and the ratio of dead space to tidal volume. The human body is very adapted and capable of eliminating CO2 from the body as excesses are produced. Essentially, unless there is a significant loss of pulmonary ventilation metabolic processes will not induce hypercapnia. [10]  Mathematically, this relationship is determined as:

PaCO2 = 0.863 x VCO2/ VA

and

VA = VE – VD

and

VE = RR x TV

and

TV = RR x dead-space volume

Where VCO2 is the metabolic production of CO2, VA is alveolar ventilation, VE is minute ventilation, VD is dead space ventilation, RR is the respiratory rate, and TV is tidal volume.

These relationships indicate that respiratory rate and tidal volume are the two components of ventilation that are physiologically or artificially controlled to moderate CO2 elimination. Therefore, a failure in either of these fields will induce hypercapnia.  It is important also to note that as PACO2 increases, oxygenation decreases. This is explained using the alveolar gas equation:

PaO2 = FiO2 (Patm – PH2O) – PaCO2 / R

Where FiO2 is the fraction of inspired oxygen (0.21 at room air), Patm is atmospheric pressure (760 mm Hg), PH20 (47 mm Hg), PaCO2 as calculated from the arterial blood gas, and R (0.8 standard value).[11][12][13]

History and Physical

The exact history and physical findings are highly variable depending on the source of hypercapnia. Patients may present with a complaint of flushed skin, lethargy, inability to focus, mild headaches, disorientation, dizziness, shortness of breath, dyspnea on exertion, nausea, vomiting, and/or fatigue. More severe complaints include confusion, paranoia, depression, abnormal muscle twitches, palpitations, hyperventilation or hypoventilation, seizures, anxiety, and/or syncope.  Often, if a patient has a known history of asthma or chronic obstructive pulmonary disease (COPD), they will know the symptoms of exacerbation and present with this as the primary complaint.

Physical exam findings are typically vague but may indicate an underlying disease. These may include fever, obesity, tachycardia, tachypnea, dyspnea, altered mental status, wheezing on auscultation, rales on auscultation, rhonchi on auscultation, decreased breath sounds, hyper-resonant chest on percussion, increased anterior-posterior diameter of chest, cardiac murmur, signs of hypoxia may be present, hepatosplenomegaly, neurological deficit, confusion, somnolence, muscular weakness, peripheral edema, asterixis, papilledema, superficial vein dilation, and/or obesity.[14][15]

Evaluation

An evaluation of hypercapnia needs to follow clinical suspicion, as the differential diagnostic list is long.  Essential tests to consider in most patients include:

• Complete blood count to determine if anemia is present.
• Complete metabolic panel to specifically evaluate sodium, potassium, and chloride as aberrations in these electrolytes are often the source of symptoms. HCO3 is also important to evaluate to determine if compensation is occurring for developing respiratory acidosis.
• Thyroid stimulating hormone to evaluate whether underlying hyperthyroidism or hyperthyroidism are present to induce thyrotoxicosis.
• An arterial or venous blood gas is possibly the most valuable laboratory test as it allows for evaluation of pH status, serum CO2, and serum HCO3. Additionally, an anion gap can be calculated to assist in determining if acidosis is metabolic or respiratory in nature. 
• Spirometry evaluates the general functioning of the lung. Forced expiratory volume over 1 second and forced vital capacity measurements are used to determine whether a restrictive or obstructive process is the etiology of hypoventilation. If air trapping is suspected, this may indicate COPD or asthmatic pathologies most commonly.
• Chest x-ray is essential in any respiratory disease evaluation to determine anatomical pathologies as well as pneumonia, pulmonary edema, among others.
• Chest CT is a more detailed radiographic evaluation and is typically used as a step up a strategy to further elucidate suspected pathology on chest x-ray.
• Echocardiography may be considered if a cardiopulmonary abnormality is suspected. Specifically, the function of the heart can be evaluated looking at the ejection fraction and valvular function.
• ECG and EMG are used to evaluate for central nervous system malfunctions and neuromuscular diseases respectively.
• Polysomnography is essential for the evaluation suspected central or obstructive sleep apnea.[16][17]

Treatment / Management

Treatment of hypercapnia should target the underlying pathology.  Direct interventions exist to assist in CO2 removal by supplementing ventilation of the lungs. These include Bi-level Positive Airway Pressure (BiPAP) ventilation assist, Continuous Positive Airway Pressure (CPAP) ventilation, and intubation with mechanical ventilation in severely ill patients. BiPAP is typically preferred in an alert, awake patient who can protect his or her airway as it allows for better air exchange between the alveolar space and atmospheric air by providing alternating levels of positive pressure support to the airway. CPAP is used in patients where there is a need for airway splinting. However, this is inferior for CO2 exchange compared to BiPAP. While technically non-invasive, these treatments are poorly tolerated due to discomfort by many patients and function as a bridging therapy to recover without more invasive measures. Mechanical ventilation is the most invasive of the listed options, but it allows the physician better control of both respiratory rate and tidal volume in addition to FiO2 and pressure support. If a patient is not alert, awake, or able to protect their airway, mechanical ventilation should be strongly considered. BiPAP, CPAP, and intubation are not curative treatments on their own, but they are supportive as stabilizing measurements while the underlying etiology is corrected. Regardless of which support is used, it is essential to optimize oxygenation status maintaining O2 saturation 90% or higher.[18][19][20](B3)

Differential Diagnosis

There is a myriad of disease pathologies that lead to hypercapnia. These include:

• Acute respiratory distress syndrome
• Asthma Exacerbation
• Central or obstructive sleep apnea
• Chronic obstructive pulmonary disorder – chronic state
• Chronic obstructive pulmonary – acute exacerbation
• Drug overdose
• Exogenous CO2 inhalation
• Head or cervical cord injury
• Myasthenia gravis
• Myxedema
• Obesity-hypoventilation syndrome (Pickwickian syndrome)
• Polyneuropathy
• Poliomyelitis
• Primary muscle disorders
• Porphyria
• Primary alveolar hypoventilation
• Pulmonary edema
• Tetanus[21][22][23]

Prognosis

Hypercapnia has a variable prognosis dependent on the exact inducing etiology. In general, younger patients have a better prognosis than older patients.